The proposed studies represent a direct outgrowth of work performed over the past two years and described in the Progress Report and accompanying publications. Hormone-receptor interactions and the relationship of these interactions to hormonal responsiveness will continue to be examined in two quite different model systems: 1) glucocorticoid receptors in rat liver will be studied with particular reference to changes induced in vivo by endogenous hormone secretion and by partial hepatectomy; and 2) beta-adrenergic receptors in the avian erythrocyte will be examined with special emphasis upon defining the mechanisms by which thyroid hormone induces the marked changes in beta-adrenergic responsiveness which we have recently reported. Studies in the first system will be directed at further characterizing the nature and physiological significance of saturable glucocorticoid binding sites in nuclear fractions from rat liver, comparison of the characteristics of nuclear and cytosol binding, and an examination of cytosol and nuclear receptor dynamics in normal and regenerating liver with particular reference to mechanisms of glucocorticoid resistance in the latter tissue. The recent development of exchange assays has made such measurements possible for the first time in the intact (i.e., non-adrenalectomized) animal. Studies in the second system will define mechanisms by which alterations induced by changes in thyroid hormone level result in striking physiologic changes in catecholamine-induced monovalent cation transport. The recent definition of marked changes in beta receptor number, adenylate cyclase activity, and intracellular cyclic AMP generation in the hyperthyroid and hypothyroid states now makes it possible to determine the specific biochemical level at which alterations in this physiologic response are induced.